A study to investigate Biomarker Effects of Pre-Surgical Treatment with DNA Damage Repair (DDR) Agents in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC).

Study identifier:D5330C00007

ClinicalTrials.gov identifier:NCT03022409

EudraCT identifier:N/A

CTIS identifier:N/A

Study Complete

Official Title

A Clinical Trial to Investigate Biomarker Effects of Pre-Surgical Treatment with DDR Agents in Patients with Head and Neck Squamous Cell Carcinoma (HNSCC) who are planned to Undergo Surgery that is likely to be followed by Radiotherapy and/or Chemotherapy.

Medical condition

Head and Neck Squamous Cell Carcinoma

Phase

Phase 1

Healthy volunteers

Study drug

Ceralasertib, Olaparib

Sex

All

Actual Enrollment

Study type

Interventional

Age

18 Years - 130 Years

Date

Study Start Date: 18 Sept 2017

Primary Completion Date: 20 Jan 2021

Study Completion Date: 20 Jan 2021

Study design

Allocation: Randomized
Endpoint Classification: Safety
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment

Verification:

Verified 01 Mar 2022 by AstraZeneca

Collaborators

Inclusion and exclusion criteria

Inclusion Criteria

· Provision of informed consent
· Aged at least 18 years
· Eastern Cooperative Oncology Group (ECOG) performance status 0,1 or 2 with no deterioration over the previous 2 weeks and an estimated life expectancy of greater than 12 weeks
· Treatment naïve HNSCC either newly diagnosed, or a second tumour at more than two years after successful treatment of the primary cancer, suitable for surgical
resection that is likely to be followed by radiotherapy and/or chemotherapy after surgery. Patients who are suitable for radical chemoradiation without surgery are
eligible if they are willing to undergo an on-treatment biopsy (FNA samples are not
acceptable, specimens must be core or surgical biopsy).
· Females must be using adequate contraceptive measures, must not be breast feeding and must have a negative pregnancy test prior to start of dosing if of child-bearing potential or must have evidence of non-child-bearing potential
· For the duration of the study and for 6 months after the last study drug administration, sexually active male patients must be willing to use barrier contraception i.e., condoms with all sexual partners
· No previous systemic cancer treatment or radiotherapy for the current malignancy
· Provision of genetics research informed consent
Pertinent

Exclusion Criteria

· Involvement in the planning and/or conduct of the study
· Previous treatment with a DDR agent
· Participation in another clinical study with an investigational product during the last 21 days or 5 half-lives of the investigational product, whichever is longer
· Receiving, or having received during the week prior to first dose, corticosteroids at a dose > 10 mg prednisone/day or equivalent for any reason
· Known hypersensitivity or contraindication to any of the investigational agents or their excipients
· Small molecule investigational medicinal products (IMPs) within 28 days prior to first dose; biological IMP within 42 days prior to first dose
· Receiving, or received, concomitant medications, herbal supplements and/or foods that significantly modulate Cytochrome P450 3A4 (CYP3A4) inhibitors or moderate Cytochrome P450, family 3, subfamily A (CYP3A) inhibitors, strong CYP3A inducers or moderate CYP3A inducers
· Impaired hepatic or renal function,inadequate bone marrow reserve or organ function
· Cardiac dysfunction defined as: Myocardial infarction within six months of study entry, New York Heart Association (NYHA) Class II/III/IV heart failure, unstable angina, unstable cardiac arrhythmias or reduced LVEF < 55%
· Any of the following cardiac criteria: Mean resting corrected QTc interval using the Fridericia formula (QTcF) greater than 450 msec/male and greater than 470 msec/female or congenital long QT syndrome, clinically important abnormalities in rhythm, conduction or morphology of resting electrocardiography (ECG), factors that increase the risk of QTc prolongation or risk of arrhythmic events, patients at risk of brain perfusion problems, relative hypotension (<100/60 mm Hg) or clinically relevant orthostatic hypotension (>20 mm Hg), uncontrolled hypertension
· Any other malignancy (i.e., non-HNSCC) which has been active or treated within the past three years (except cervical intra-epithelial neoplasia and non-melanoma skin cancer)
· Patients unable to swallow orally administered medication and patients with gastrointestinal disorders likely to interfere with absorption of the study medication
· Patients considered a poor medical risk due to a serious, uncontrolled medical disorder, non-malignant systemic disease or active, uncontrolled infection
· Judgement by the Investigator that the patient should not participate in the study
· Patients with myelodysplastic syndrome (MDS)/acute myeloid leukaemia (AML) or with features suggestive of MDS/AML
· Previous allogenic bone marrow transplant or double umbilical cord blood transplantation (dUCBT)
· Non-leukocyte depleted whole blood transfusion within 120 days of the date of patient's start on the study

Location

Research Site

Pittsburgh, PA, United States, 15213

Location

Research Site

Toulouse, France, 31300

Location

Research Site

Taipei, Taiwan, Province of China, 100

Location

Research Site

Pittsburgh, PA, United States, 15261

Arms	Assigned Interventions
Experimental: AZD6738 AZD6738 (160 mg) tablet twice daily continuous dosing for a minimum of 9 days and a maximum of 21 days.	Drug: Ceralasertib Ceralasertib is an oral agent and will be dosed at 160 mg. Ceralasertib tablets should be taken at the same time each day, approximately 12 hours apart (maximum ± 2 hour window) with one glass of water. Ceralasertib is a potent, selective inhibitor of the serine/threonine-specific protein kinase, ataxia telangiectasia and Rad3-related protein (ATR), with good selectivity against other phosphatidylinositol 3-kinase-related kinase (PIKK) family members. Other Name: AZD6738
Experimental: Olaparib Olaparib (300 mg) tablets administered orally twice daily continuously for a minimum of 9 days and a maximum of 21 days.	Drug: Olaparib Olaparib is available as a green film-coated tablet containing 100 mg or 150 mg of Olaparib. Patients will be administered Olaparib orally twice daily at 300 mg bid. The Olaprib tablets should be taken at the same time each day, approximately 12 hours apart with one glass of water. Olaparib (AZD2281, KU-0059436) is a potent Polyadenosine 5’diphosphoribose [poly (ADP ribose)] polymerisation (PARP) inhibitor (PARP-1, -2 and -3) that is being developed as an oral therapy, both as a monotherapy (including maintenance) and for combination with chemotherapy and other anti-cancer agents. Other Name: AZD2281

Arms

Assigned Interventions

Experimental: AZD6738
AZD6738 (160 mg) tablet twice daily continuous dosing for a minimum of 9 days and a maximum of 21 days.

Drug: Ceralasertib
Ceralasertib is an oral agent and will be dosed at 160 mg. Ceralasertib tablets should be taken at the same time each day, approximately 12 hours apart (maximum ± 2 hour window) with one glass of water. Ceralasertib is a potent, selective inhibitor of the serine/threonine-specific protein kinase, ataxia telangiectasia and Rad3-related protein (ATR), with good selectivity against other phosphatidylinositol 3-kinase-related kinase (PIKK) family members.

Other Name: AZD6738

Experimental: Olaparib
Olaparib (300 mg) tablets administered orally twice daily continuously for a minimum of 9 days and a maximum of 21 days.

Drug: Olaparib
Olaparib is available as a green film-coated tablet containing 100 mg or 150 mg of Olaparib. Patients will be administered Olaparib orally twice daily at 300 mg bid. The Olaprib tablets should be taken at the same time each day, approximately 12 hours apart with one glass of water. Olaparib (AZD2281, KU-0059436) is a potent Polyadenosine 5’diphosphoribose [poly (ADP ribose)] polymerisation (PARP) inhibitor (PARP-1, -2 and -3) that is being developed as an oral therapy, both as a monotherapy (including maintenance) and for combination with chemotherapy and other anti-cancer agents.

Other Name: AZD2281

Documents available

Redacted CSR Synopsis
Download
Trial Results Summaries
Available here

Contacts

Contact

AstraZeneca Clinical Study Information Center

1-877-240-9479

information.center@astrazeneca.com

Investigators

Principal Investigator

Dr. Umamaheshwar Duvvuri

University of Pittsburgh Medical Center (UPMC)

Sponsors

Collaborators

Inclusion Criteria

Exclusion Criteria

Research Site

Research Site

Research Site

Research Site

Redacted CSR Synopsis

Trial Results Summaries